Wound healing and maintenance of immune function are among the most important priorities of the severely injured organism. This study will examine how the two responses are interrelated. While lymphocyte influx into the wound is a constant occurrence, the effect of T lymphocytes on the healing process is unclear. We hypothesize that: 1) T lymphocytes first stimulate wound healing by promoting fibroblast migration, replication and collagen synthesis; 2) as healing progresses, wound T lymphocytes are "de- activated" and down-regulate fibroblast activity, either by removing the positive stimulus described in 1 or by secreting fibroblast-inhibitory lymphokines. This hypothesis will be tested by: a) using monoclonal antibodies to morphologically characterize the dynamics of T lymphocyte migration into wounds at the site of healing; b) harvesting wound T lymphocytes at different times post-wounding and determining the subsets present; c) studying the effect of purified wound T lymphocyte subsets harvested at various times post-wounding on in vitro fibroblast activity (replication, chemotaxis, collagen synthesis); d) administering in vivo cytotoxic monoclonal antibodies against all T lymphocytes, the helper/effector or the suppressor/cytotoxic; these in vivo depletions will be carried out pre-wounding (therefore removing the stimulatory stimulus) or at various times post-wounding, thereby removing the inhibitory one; wound healing will be tested by the wound breaking strength and reparative collagen deposition. As a corrolary of the above hypothesis, the mechanism by which wound lymphocytes are deactivated will be studied. We have found that fluid obtained from 10 day old wounds inhibits lymphocyte immune responses in vitro and in vivo rejection of allogeneic grafts. The wound fluid factor impairs IL2-dependent responses in vitro. The cytokine appears to be produced by infiltrating wound mononuclear cells which can also impair in vitro mitogenic and allogeneic responses. The appearance of these inhibitory mononuclear cells and the generation of lymphocyte-inhibitory cytokine may have the beneficial effect of down-regulating lymphocyte-driven fibroblast activity and thus modulate the healing response. We postulate that this inhibitory cytokine may affect host immune responses if the trauma is severe and, perhaps, explain the immunesuppression observed in major injuries. This will be tested by examining the in vivo mechanism of action of wound fluid on host immune responses.